This program is directed towards the molecular processes involved in the mutagenic and lethal effects of light, with emphasis on identifying the fast initial photolysis steps and relating them to the permanent damage. Catenase enzymes of known tertiary structure and specificities are being employed as model systems which display photochemical properties characteristic of biologic macromolecules with an active site region and damage dependent conformation. Ultraviolet irradiation effects are being studied with flash photolysis, augmented by measurements of fluorescence, action spectra, and residue destruction. The current work on lysozyme, RNase, trypsin and papain will be extended to the enzyme-substrate and enzyme-inhibitor complexes and new investigations will be initiated on metalloenzymes. The primary processes of interest include electron ejection from aromatic residues to the medium, intramolecular electron and energy transfer, and biphotonic photolysis. Current work on photodynamic inactivation of lysozyme will be extended to other enzymes and to sensitization by medicinals and drugs. The damaging role of singlet oxygen and the influence of sensitizer-protein complexing on its effectiveness will be studied with photostationary measurements of transient intermediates, steady irradiation quantum yields, and fluorescence analysis of dye and drug binding interactions. The essential results should be applicable to other proteins including repair enzymes and nucleoproteins. Singlet oxygen generated by sensitization can attack proteins, DNA and lipid membranes and may be involved in light-induced diseases such as prophyrias, the photodynamic syndrome, and certain skin cancers.